The University of Alabama at Birmingham is a public university in Birmingham in the U.S. state of Alabama. Developed from an academic extension center established in 1936, the institution became an autonomous institution in 1969 and is today one of three institutions in the University of Alabama System. In the fall of 2013, 18,568 students from more than 110 countries were enrolled at UAB pursuing studies in 140 programs of study in 12 academic divisions leading to bachelor's, master's, doctoral, and professional degrees in the social and behavioral science, the liberal arts, business, education, engineering, and health-related fields such as medicine, dentistry, optometry, nursing, and public health.The UAB Health System, one of the largest academic medical centers in the United States, is affiliated with the university. UAB Hospital sponsors residency programs in medical specialties, including internal medicine, neurology, surgery, radiology, and anesthesiology. UAB Hospital is the only ACS verified Level I trauma center in Alabama, as rated by the American College of Surgeons Trauma Program.UAB is the state's largest employer, with more than 18,000 faculty and staff and over 53,000 jobs at the university and in the health system. An estimated 10 percent of the jobs in the Birmingham-Hoover Metropolitan Area and 1 in 33 jobs in the state of Alabama are directly or indirectly related to UAB. The university's overall annual economic impact was estimated to be $4.6 billion in 2010. Wikipedia.
Zhou D.,University of Alabama at Birmingham
Nature genetics | Year: 2010
We show that knockdown of KLF1 in human and mouse adult erythroid progenitors markedly reduces BCL11A levels and increases human gamma-globin/beta-globin expression ratios. These results suggest that KLF1 controls globin gene switching by directly activating beta-globin and indirectly repressing gamma-globin gene expression. Controlled knockdown of KLF1 in adult erythroid progenitors may provide a method to activate fetal hemoglobin expression in individuals with beta-thalassemia or sickle cell disease.
Tolwani A.,University of Alabama at Birmingham
New England Journal of Medicine | Year: 2012
Acute limb ischemia due to a perioperative type B (distal) thoracic aortic dissection develops in a 90-kg, 20-year-old man with Marfan's syndrome who is admitted to the hospital for elective aortic-valve replacement. On postoperative day 1, he undergoes endovascular repair of the thoracic aorta. On postoperative day 4, his urine output decreases to 420 ml over a 24-hour period. He requires mechanical ventilation with a fraction of inspired oxygen (FIO2) of 0.70; his mean arterial pressure is 74 mm Hg with vasopressor support. He has had a positive fluid balance of 9.8 liters since admission. The serum creatinine level has increased from a baseline of 0.6 mg per deciliter (53.0 μmol per liter) to 4.4 mg per deciliter (389.0 μmol per liter). The bicarbonate level is 19 mmol per liter despite bicarbonate infusion, and the potassium level is 6.1 mmol per liter. The creatine kinase level has increased to 129,040 U per liter. An intensive care specialist evaluates the patient and recommends initiation of continuous renal-replacement therapy. Copyright © 2012 Massachusetts Medical Society.
Wang J.,University of Alabama at Birmingham
Cold Spring Harbor perspectives in biology | Year: 2012
Wnts are evolutionarily conserved signaling ligands critical for animal development. Genetic engineering in the mouse has enabled investigators to acquire a detailed activation profile of the β-catenin-dependent canonical Wnt pathway during mouse development, and to manipulate Wnt pathway activities with great spatial and temporal precision. Together, these studies have not only revealed important functions of Wnt signaling at multiple stages of early mouse development, but also elucidated how the Wnt pathway interacts with other pathways to form signaling networks that confer the unique features of mammalian embryogenesis. Additionally, the planar cell polarity pathway has emerged as an essential β-catenin independent noncanonical Wnt pathway that coordinates cell polarity and regulates tissue morphogenesis in various mammalian developmental processes. Importantly, studies of Wnt signaling in mouse development have also revealed important pathogenic mechanisms of several congenital disorders in humans.
Roberson E.D.,University of Alabama at Birmingham
Annals of Neurology | Year: 2012
The pace of discovery in frontotemporal dementia (FTD) has accelerated dramatically with the discovery of new genetic causes and pathological substrates of the disease. MAPT/tau, GRN/progranulin, and C9ORF72 have emerged as common FTD genes, and TARDBP/TDP-43, VCP, FUS, and CHMP2B have been identified as less common genetic causes. TDP-43 and FUS have joined tau as common neuropathological substrates of the disease. Mouse models provide an important tool for understanding the role of these molecules in FTD pathogenesis. Here, we review recent progress with mouse models based on tau, TDP-43, progranulin, VCP, and CHMP2B. We also consider future prospects for FTD models, including developing new models to address unanswered questions. There are also opportunities for capitalizing on conservation of the salience network, which is selectively vulnerable in FTD, and the availability of FTD-related behavioral paradigms to analyze mouse models of the disease. Ann Neurol Copyright © 2012 American Neurological Association.
Calhoun D.A.,University of Alabama at Birmingham
Annual Review of Medicine | Year: 2013
Resistant hypertension affects an estimated 10-15 million American adults and is increasing in prevalence. The etiology of resistant hypertension is almost always multifactorial, including obesity, older age, high dietary salt, chronic kidney disease, and aldosterone excess. Classical primary aldosteronism and lesser degrees of aldosterone excess, possibly originating from visceral adipocytes, contribute broadly to antihypertensive treatment resistance. Treatment of resistant hypertension is predicated on appropriate lifestyle changes and use of effective combinations of antihypertensive agents from different classes. Blockade of aldosterone with spironolactone has been shown to be particularly effective for treatment of resistant hypertension. The antihypertensive benefit of spironolactone is not limited to patients with demonstrable hyperaldosteronism but instead can be effective in resistant hypertensive patients regardless of aldosterone levels. Chlorthalidone is a potent, long-acting thiazide-like diuretic and should be used preferentially to treat resistant hypertension as it is superior to normally used doses of hydrochlorothiazide. Copyright © 2013 by Annual Reviews.
Carroll S.L.,University of Alabama at Birmingham
Acta Neuropathologica | Year: 2012
Neurofibromas, schwannomas and malignant peripheral nerve sheath tumors (MPNSTs) all arise from the Schwann cell lineage. Despite their common origin, these tumor types have distinct pathologies and clinical behaviors; a growing body of evidence indicates that they also arise via distinct pathogenic mechanisms. Identification of the genes that are mutated in genetic diseases characterized by the development of either neurofibromas and MPNSTs [neurofibromatosis type 1 (NF1)] or schwannomas [neurofibromatosis type 2 (NF2), schwannomatosis and Carney complex type 1] has greatly advanced our understanding of these mechanisms. The development of genetically engineered mice with ablation of NF1, NF2, SMARCB1/INI1 or PRKAR1A has confirmed the key role these genes play in peripheral nerve sheath tumorigenesis. Establishing the functions of the NF1, NF2, SMARCB1/INI1 and PRKAR1A gene products has led to the identification of key cytoplasmic signaling pathways promoting Schwann cell neoplasia and identified new therapeutic targets. Analyses of human neoplasms and genetically engineered mouse models have established that interactions with other tumor suppressors such as TP53 and CDKN2A promote neurofibroma-MPNST progression and indicate that intratumoral interactions between neoplastic and non-neoplastic cell types play an essential role in peripheral nerve sheath tumorigenesis. Recent advances have also provided new insights into the identity of the neural crest-derived populations that give rise to different types of peripheral nerve sheath tumors. Based on these findings, we now have an initial outline of the molecular mechanisms driving the pathogenesis of neurofibromas, MPNSTs and schwannomas. However, this improved understanding in turn raises a host of intriguing new questions. © 2011 Springer-Verlag.
West A.B.,University of Alabama at Birmingham
Movement Disorders | Year: 2015
The burden that Parkinson's disease (PD) exacts on the population continues to increase year after year. Though refinement of symptomatic treatments continues at a reasonable pace, no accepted therapies are available to slow or prevent disease progression. The leucine-rich repeat kinase 2 (LRRK2) gene was identified in PD genetic studies and offers new hope for novel therapeutic approaches. The evidence linking LRRK2 kinase activity to PD susceptibility is presented, as well as seminal discoveries relevant to the prosecution of LRRK2 kinase inhibition. Finally, suggestions are made for predictive preclinical modeling and successful first-in-human trials. © 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Beukelman T.,University of Alabama at Birmingham
Arthritis and rheumatism | Year: 2012
To determine the relative rates of incident malignancy among children with juvenile idiopathic arthritis (JIA) with respect to treatment as compared to children without JIA. Using national Medicaid data from 2000 through 2005, we identified cohorts of children with JIA and without JIA according to the diagnosis codes used by their physicians and the medication prescriptions that were dispensed. Study followup began after a 6-month lag period to exclude prevalent and misdiagnosed malignancies. Treatment with methotrexate (MTX) and tumor necrosis factor (TNF) inhibitors was categorized as ever exposed or never exposed. Malignancy outcomes were identified using an adapted version of a previously validated algorithm. Incident malignancies were categorized as possible, probable, or highly probable based on a comprehensive review of all claims. Malignancy rates were standardized to the age, sex, and race distribution of the overall JIA cohort. Standardized incidence ratios (SIRs) were calculated using children with attention deficit hyperactivity disorder (n = 321,821) (one of two comparator groups included) as the referent group. The JIA cohort included 7,812 children with a total followup time of 12,614 person-years; 1,484 of these children contributed 2,922 person-years of TNF inhibitor exposure. For all children with JIA versus children without JIA, the SIR was 4.4 (95% confidence interval [95% CI] 1.8-9.0) for probable and highly probable malignancies. For those taking MTX without TNF inhibitor use, the SIR was 3.9 (95% CI 0.4-14). Following any use of TNF inhibitors, no probable or highly probable malignancies were identified (SIR 0 [95% CI 0-9.7]). Children with JIA appeared to have an increased rate of incident malignancy compared to children without JIA. The treatment for JIA, including TNF inhibitors, did not appear to be significantly associated with the development of malignancy. Copyright © 2012 by the American College of Rheumatology.
Agency: NSF | Branch: Standard Grant | Program: | Phase: BIOMEDICAL ENGINEERING | Award Amount: 299.86K | Year: 2017
In 2015, cancer caused at least 0.5 million deaths and 1.5 million new cases were diagnosed in the US. The adoptive transfer of large numbers of tumor-infiltrating T cells or genetically engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. The existing methods to manufacture large quantities of such human T cells, however, have severe limitations of low efficiency, inconsistency and lack of sufficient quality control. This EAGER proposal aims to develop a novel human T cell biomanufacturing platform for large-scale, robust, and high-quality cellular production. The accomplishment of this study will provide not only the proof-of-concept but also the ready-to-use bioproduction platform for new means of T cell expansion for clinical immune cancer therapy. The novel technology employed in the rational production process engineering will also be able to provide guidelines and apply easily to the manufacturing of other therapeutic cells. Whereas the results and knowledge obtained in this study will be useful for both the biopharmaceutical industry and academic research, all cancer patients may benefit from the products of this research project.
The primary goal of this proposal is to develop an entirely new, metabolic cell process engineering (MCPE)-based, cellular biomanufacturing platform using stirred-tank bioreactor to produce reliable and reproducible large quantities of human T cells for immune cancer therapy, aiming to effectively produce more than 2,000 million T cells with high quality. The traditional T cell biomanufacturing presents several weaknesses: 1) low efficiency of mass transfer that often results in heterologous cellular metabolism, cell viability and product quality; 2) ineffective process parameter control that causes low robustness, reliability and scalability; and 3) lack of critical quality attributes in the early and middle stages of process development, limiting the application of quality by design. This project focuses on developing an innovative stirred-tank-based cellular biomanufacturing platform to produce reliable and reproducible large quantities of human T cells (or CAR T cells) for immune cancer therapy. Supported by Design of Experiment (DoE), proteomics and metabolomics will be applied to evaluate and determine the key bioproduction process parameters (such as stirred-tank parameters, media, supplements, etc.) to control T cell metabolism and cell growth. The oxygen transfer coefficient-based scale-up strategy will be developed to guide large-scale manufacturing of T cells, which will be validated using small- and medium- size tank bioreactors with scale-up factor of 10. In addition, at multiple key steps of the cellular bioproduction, the T cell quality control will be established via monitoring and evaluating cellular density, viability, T cell surface markers and functions. The existing T cell biomanufacturing in flask, LifeCell bag or Wave bag is limited by the weaknesses of lot-to-lot variation, heterologous product quality during scale-up, and low reproducibility. The proposed approach, i.e. MCPE-based fed-batch T cell production in stirred-tank bioreactor, that enables homogenous cell expansion, high cell density, high viability and good product quality in large-scale T cell manufacturing would be a major methodological advance for the field. Moreover, the systems biology approach will help advance the knowledge of host cell protein expression and intracellular metabolite profiling of human T cells under various culture conditions. In addition, the liquid activators in this proposed strategy will avoid heterologous suspension culture, improve cell growth efficiency, simplify manufacturing operation and reduce production cost. The critical scale-up factors learned from this application will guide future large-scale T cell biomanufacturing. Finally, the quality control at multiple stages of the process development will help identify potential product quality and process scale-up pain points during T cell bioproduction. To the PIs best knowledge, this is the first effort to rationally develop T cell bioproduction process via understanding the interaction between cellular metabolism and process parameters.
Agency: NSF | Branch: Continuing grant | Program: | Phase: FED CYBER SERV: SCHLAR FOR SER | Award Amount: 805.55K | Year: 2017
This project seeks to establish a new CyberCorps®: Scholarship for Service (SFS) program at the University of Alabama at Birmingham to prepare highly-qualified Cybersecurity professionals for entry into the federal, state, local, and tribal government workforce. The proposal addresses the growing need for a well-trained cyber-security workforce via a unique partnership between Computer and Information Sciences (CIS) and Justice Sciences (JS). This proposal supports the U.S. Department of Justices call to develop new tools and applications that improve the capacity to use and process digital evidence. The key to these goals is to educate the next generation of cybersecurity professionals skilled in the use of these new tools and processes. The project will provide SFS students with knowledge and practical experience on how to conduct cyber-criminal investigations. The graduates will develop unique skills to combat cyber-crime. The proposed combination of CIS and JS creates a unique model of cross-disciplinary education and research to address cyber-crime. The program aims to produce unique professionals serving in the public sector and it could serve as an exemple for other universities. The project will employ mechanisms to enroll students from minority populations and to retain them via innovative approaches focused on monitoring and mentoring. The project emphasizes outreach to high school students via security events and summer camps, the Intelligence Community via internships, the public via security conferences and workshops, as well as the media. It will contribute to improve national security and online safety by graduating highly-skilled cybersecurity professionals who are dedicated to public service.
The university is designated as the DHS/NSA Center of Academic Excellence in Cyber Defense Research, and the proposed program is leveraging the existing Masters program in Computer Forensics and Security Management (CFSM) offered jointly by CIS and JS. A minimum of 30 semester hours of credit are required for the MS-CFSM degree, including 21 hours of required credits and 9 hours of elective credits fulfilled by choosing one of two tracks in the program: Cybercrime Investigations or IT Audit/Fraud Examination. The courses offered within the program include Computer Network Security; Information Security Management; Ethics and Computer Forensics; Law Evidence and Procedure; Malware Analysis; and Fraud Examination; among several other offerings. The team has a close working relationship with federal organizations, including formal internship agreements, and cybersecurity research support from NSF, DARPA, IARPA, ONR, DHS, NIJ, COPS, BJA, the state of Alabama, and federal law enforcement agencies, including the FBI and ICE.